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Figure 1 Target populations and outcomes in the course of pregnancy for diagnostic research on spontaneous preterm birth Gestational age (weeks) 20 30 34 37 40 Preterm Term Asymptomatic women singleton gestation in early pregnancy Symptomatic women late (viable) pregnancy Spontaneous preterm birth Neonatal complications e.g. disability, mortality 29 Early pregnancy Late (viable) pregnancy
The second population of interest is that of symptomatic women with singleton gestation who present with threatened preterm labour. For these women, there is a need to identify those who will go on to deliver prematurely as the key clinical decisions following testing relates to immediate management and outcome. For example, if cervico-vaginal fetal fibronectin testing could predict spontaneous preterm birth among these women before advanced cervical dilatation, 23 antenatal maternal intramuscular corticosteroid injection may be administered to accelerate fetal lung maturity to prevent respiratory distress syndrome. 24 In-utero transfer to a tertiary intensive neonatal care unit able to care for the premature neonate may also be considered. 25;26 Such a transfer, which may take some time to arrange (because of logistics, geography or lack of neonatal intensive care cots), would be inappropriate if birth were imminent, as this would risk delivery en-route. In such cases, knowledge of a higher likelihood of imminent birth may allow rational use of tocolytics agents, which aim to suppress or diminish contractions allowing time for antenatal corticosteroid administration to exert its beneficial effects. 27 Antenatal corticosteroids have maximal effectiveness in preventing neonatal complications of prematurity delivered within 2-7 days after administration. 24 Given the duration of time required for corticosteroids to exert beneficial effects and the potential for in-utero transfer and tocolytic administration, knowledge of impending birth within 48 hours to 7 days of testing would be a clinically meaningful outcome measure among women symptomatic of threatened preterm labour. 30
Page 1 and 2: ACCURACY OF TESTS FOR PREDICTING SP
Page 3 and 4: Abstract Spontaneous preterm birth
Page 5 and 6: Acknowledgements In undertaking thi
Page 7 and 8: Table of contents Chapter 1 Thesis
Page 9 and 10: Absence of fetal breathing movement
Page 11 and 12: Figure 15 Forest plots of likelihoo
Page 17 and 18: eference standards (outcome of spon
Page 19 and 20: Table 18 Individual accuracy result
Page 21 and 22: Table 48 Characteristics of test ac
Page 23 and 24: labour. Literature was identified f
Page 25 and 26: 8) strategies needs to be explored.
Page 27 and 28: morbidities, which often lengthen h
Page 29: anticipating a normal course of pre
Page 33 and 34: Chapter 3 Methods Protocol developm
Page 35 and 36: stage process using predefined and
Page 37 and 38: Table 1 List of tests that purporte
Page 39 and 40: corresponding authors so that only
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Page 43 and 44: Figure 3 Identification of test acc
Page 45 and 46: with one previous spontaneous prete
Page 47 and 48: Figure 6 Plot of sensitivity agains
Page 49 and 50: predicting spontaneous preterm birt
Page 51 and 52: Figure 9 Forest plots of likelihood
Page 53 and 54: within 7-10 days of testing in addi
Page 55 and 56: Figure 10 Methodological quality of
Page 57 and 58: Figure 13 Plot of sensitivity again
Page 63 and 64: Cervico-vaginal prolactin During pr
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Page 75 and 76: Serum α-fetoprotein (MSAFP) A high
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Accuracy of maternal serum relaxin
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Figure 38 Forest plots of likelihoo
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Only two studies used the same thre
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β-human chorionic gonadotrophin (
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showed asymmetry indicating presenc
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Estriol Estriol is produced by both
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Figure 46 Methodological quality of
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while for symptomatic women with th
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Interleukin-6 (IL6) Interleukin 6 (
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epresented the largest higher quali
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Figure 57 Plot of sensitivity again
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two-weekly interval. For symptomati
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Matrix metalloproteases-9 (MMP-9) D
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All but one study assessed women’
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Asymptomatic bacteriuria assessment
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Gram staining using Spiegel’s 232
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Mammary stimulation test Antenatal
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Uterine activity monitoring Presenc
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Accuracy of uterine activity monito
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Rheobase Rheobase in the context of
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Absence of fetal breathing movement
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Cervical ultrasound assessment Ante
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Accuracy of cervical length and fun
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gestation or birth with 48 hours of
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The main accuracy results are summa
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Figure 100 Summary forest plots of
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Screening typically involves use of
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Table 3 Summary of tests’ accurac
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Table 5 Summary of tests’ accurac
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Chapter 6 Discussion Methodological
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completely as would have been desir
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antenatal women population, using a
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final common pathway of spontaneous
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effectiveness), there are no practi
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Recommendations for research • Ne
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modelling project should make provi
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188
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Appendix II - Search strategies MED
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111. (premature adj3 rupture adj3 m
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92. Granuloma Inguinale/ 93. mycopl
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s (oncofetal or c-reactive)(w)(prot
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s (uterine or antepartum)(3w)(hemor
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interpregnancy and interval* or occ
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((((physical next exam) or (physica
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Appendix IV - Characteristics and r
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Table 12 Characteristics of test ac
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Table 13 Individual accuracy result
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Table 14 Characteristic of studies
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Symptomatic Luzzi 110 2003 133 Coho
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Peaceman 79 1997 725 Cohort Prospec
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Rozenberg 128 1997 76 Calda 120 199
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Elizur 144 2005 35 Cohort Prospecti
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Table 21 Characteristics of the inc
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Table 23 Characteristics of studies
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Liu 183 1999 USA 72 Case-control Re
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*TP = true positive, FP = false pos
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Silver 219 1993 USA 29 Cohort Prosp
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Turhan 230 2000 Turkey 82 Cohort Pr
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34 weeks Rizzo 1 217 18 0 34 40 0.3
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Stuart 273 1965 UK 817 Case-control
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Helou, 1996 292 Israel Cohort Blind
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Krohn, 1991 302 USA Prospective Tes
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Holst 232 Spiegel 9 3 13 24 0.41 0.
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Castle 312 1983 English Cohort Pros
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Another method for assessing hetero
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Publications directly contributing
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15. Martin JA, Hamilton BE, Sutton
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44. Honest H, Bachmann LM, Knox EM,
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72. Parikh MN,.Mehta AC. Internal c
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99. Vercoustre L, Sotter S, Bouige
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126. Pieta-Dolinska A, Jaczewski B,
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preterm delivery but not with fetal
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and activin A in maternal serum: pr
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199. Foulon W, Van Liedekerke D, De
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223. Kurkinen-Raty M, Ruokonen A, V
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249. Radnai M, Gorzo I, Nagy E, Urb
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281. Spiegel CA, Amsel R, Eschenbac
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307. Guinn DA, Wigton TR, James JA,
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334. Daskalakis G, Thomakos N, Hatz
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